Over the last decade, medicine has undergone a profound and rapid change as a result of advances in cellular and molecular biology. Discoveries resulting from the sequencing of the human genome, and a better understanding of metabolism and physiology have contributed to the evolution of "molecular medicine". Significant improvements in medicine have depended upon the translation of new discoveries from the bench-top into animal models and then into clinical trials. Recognizing the key role of rats and mice, especially transgenic mice, as models for molecular biology, genetics and experimental therapeutics, the bioengineering community has focused on the development of miniaturized CT, MRI and PET devices optimized for use with small animals. Several such instruments are now commercially available, which promises to have a major impact on biomedical research. Expanded access to these devices will contribute greatly to the rapid improvement in understanding and treatment of human disease. Several recent NIH initiatives have underscored the importance of developing imaging laboratories that would take advantage of small animal research models. By allowing non-invasive, in vivo evaluation of biochemistry and pharmacokinetics, PET imaging could have substantial utility in evaluating new drugs and treatment strategies. Unfortunately, the applicability of clinical PET devices for preclinical studies with laboratory animals is restricted because the spatial resolution is too coarse relative to the sizes of rats and mice, the predominant animal models. A miniaturized, small animal PET device, offering image resolution on the order of 1-2 mm, would permit detailed, quantitative studies in subjects as small as a mouse. Strong collaborations have been forged between the USC PET Imaging Science Center and the many investigators at USC who are at the forefront of basic biological science in the areas of molecular biology, gene therapy and experimental therapeutics. The primary impediment to the growth of functional imaging within these relationships is the current lack of non-invasive functional imaging, which would permit the measurement of the dynamic metabolic and pharmacologic processes of interest, as well as enable serial monitoring of tumor growth and treatment response within the same laboratory animal. A small animal PET imaging device is requested in this shared instrumentation proposal. USC has the leadership, scientific investigators, equipment and facilities necessary to provide an environment in which the potential benefits of a small animal PET scanner can be fully realized.